Table 2.

Combination therapy to overcome resistance to checkpoint inhibitor

Mechanism of resistance	Potential combination therapy
Low mutation burden/lack of neo-antigens	ICI + radiation              ICI + chemotherapy              ICI + oncolytic virus
T-Cell Exclusion program	ICI + CDK4/6 inhibitor
Defects in antigen processing/β2M	ICI + interferon
VEGF production by tumor	ICI + VEGF inhibitor
Epigenetic modulation leading to decrease in tumor antigenicity	ICI + hypo-methylating agent              ICI + HDAC inhibitors
Secondary checkpoints	ICI + anti-TIM3              ICI + anti-TIGIT
Immunosuppressive cells in tumor microenvironment	ICI + PI3K-γ selective inhibitor              ICI + HDAC inhibitor              ICI + anti-CSF1R
Inhibitory molecules and cytokines	ICI + IDO-1 inhibitor              ICI + anti-CD73mab              ICI + TGF-β receptor kinase

ICI: Immune checkpoint inhibitors; VEGF: vascular endothelial growth factor; HDAC: histone deacetylase; TGF: tumor growth factor